Colorectal cancer is the second-leading cause of cancer-related deaths in the United States (11). Each year, approximately 150,000 people are diagnosed with colorectal cancer and almost 60,000 people die from the disease. Of those diagnosed, nearly half are expected to die within five years, since most cancers are detected when the cancer is less treatable. For those whose cancer is detected at an earlier stage, the five-year survival rate can be greater than 90%. The American Cancer Society recommends that all Americans age 50 and older be screened regularly for colorectal cancer. Unfortunately, only a fraction of this population is screened for the disease, as currently available screening technologies are considered as either too costly, and/or too invasive or in some cases insufficiently accurate.
Most colorectal cancers begin as small, noncancerous (benign) clumps of cells called polyps. Over time some of these polyps become cancerous. Incidence of polyps increase as individuals get older. It is estimated that 50% of the people over the age of 60 will have at least one polyp.
The significance of identifying one or more colorectal pathologies including polyps is that certain types of polyps are cancerous or indicative of an increased risk to develop cancer. It has been shown that the removal of certain subtypes of polyps reduces the risk of getting colorectal cancer significantly. Therefore, a test to screen for one or more colorectal pathologies including polyps and/or certain subtypes of polyps so as to allow early removal or to prevent unnecessary procedures should markedly reduce the incidence of colorectal cancer (12) and decrease the current costs to the medical system.
Currently utilized screening technologies to identify polyps include 1) a fecal occult blood test (FOBT); 2) a flexible sigmoidoscopy; 3) double contrast barium enema (DCBE); and 4) colonoscopy. Sometimes two or more of these tests are used in combination. The current recommended standards for screening for colorectal cancer in men over the age of 50 and who are considered part of an average risk population include: an FOBT yearly, a sigmoidoscopy every five years, a colonoscopy every ten years and a DCBE every five years. For a high risk population where one or more family members have had colorectal cancer, a colonoscopy is recommended every two years as a follow up to FOBT or sigmoidoscopy.
Each of these tests suffers significant disadvantages. FOBT testing, although a non-invasive procedure, requires significant dietary and other restrictions prior to testing and suffers from a low sensitivity. Sigmoidoscopy and colonoscopy are more sensitive since they involve direct visualization of the lumen, however, sigmoidoscopy only allows partial visualization, and the colonoscopy is known to miss about 12% of advanced adenomas. Both sigmoidoscopy and colonoscopy are highly invasive procedures which cause high levels of discomfort causing many individuals to opt not to undergo these recommended screening procedures. Also sigmoidoscopy and colonoscopy are costly, and may have complications which arise as a result of undergoing the procedure.
Thus, there is a need for an improved test which is minimally invasive so as to permit more widespread testing of the population to indicate the presence of one or more colorectal pathologies, and ensure greater adherence to recommended protocols. To date, despite this need, there have been very few advancements in identifying useful molecular biomarkers to test for colorectal pathology. Recent efforts have focused on DNA based biomarker methods (see for example Shuber et al. U.S. Patent Application Publication No. 2005-0260638A1; or Lofton-Day et al. WO2005/001142).
Identification of biomarkers for use in a non-invasive test for colorectal pathology thus fulfills a longstanding need in the art.